Efficacy of Lenalidomide With Rituximab in Refractory or Relapse of Primary Central Nervous System Lymphoma

Inclusion Criteria:

1. Patients over 18 years old with a refractory or relapse PCNSL and who have previously received at least high dose methotrexate (\> 1.5 g/m²) and high dose cytarabine (2 g/m²).
2. Patients can have received radiotherapy or intensive chemotherapy with hematopoietic stem cell rescue as part of treatment of the PCNSL or IOL
3. Patients over 18 years old with a refractory or relapse IOL and who have received either intravenous high dose methotrexate (\> 1.5 g/m2) or intraocular methotrexate
4. Life expectancy \> 2 months
5. Able to swallow capsules (stomach tube not allowed)
6. Adequate bone marrow function with absolute leukocytes \> 2000/mm3, neutrophil count (ANC) \> 1000/mm3, haemoglobin \> 8 g/dl and platelets \> 100 000/mm3
7. Adequate liver function with Serum SGOT/AST or SGPT/ALT \< 3.0 X Upper Limit of Normal ULN ; bilirubin \< 1.5 X LNS (excepted in case of hemolytic anemia or Gilbert's syndrome)
8. Calculated creatinine clearance \> 40 ml/min. Patients with calculated creatinine clearance between 40 and 50ml/min lenalidomide dose will be adjusted as follows (10mg once daily)
9. Patient aged 18 years old or more and without measure of legal protection
10. Able to understand teratogenic risks of the treatment
11. Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual contact during the following time periods related to this study for at least four weeks before starting study drug, while participating in the studyand for at least 4 weeks after discontinuation of Lenalidomide and 1 year after Rituximab.. Pregnancy tests (serum β-HCG dosage) will be negative at baseline and during the study. Men must agree not to procreate a child and use condoms if their partner can procreate, during all the treatment period, during dose interruptions and for at least 4 weeks after study drug discontinuation.
12. Signed inform consent

Exclusion Criteria:

1. Contraindication to any drug contained in the chemotherapy regimen or to any of their excipients
2. T-cell lymphoma
3. Diagnosis of any second malignancy within the last 5 years
4. Prior history of organ transplantation or other cause of severe immunodeficiency
5. History of heart disease and/or impaired cardiac function (ECG QTc\>450msec, congenital long QT syndrome, history of ventricular tachyarrhythmia, ventricular fibrillation, congestive heart failure NYHA III/IV, uncontrolled hypertension).
6. Known HIV or HTLV-1 infection, positive serology to HB surface antigen \[HBsAg\] or total HB core antibody \[anti-HB-c\]) and Hepatitis C (Hepatitis C virus \[HCV\] antibody) not older than 4 weeks
7. Inclusion in another experimental anti-cancer drug therapy\*
8. Impossibility to follow the calendar of exams because of geographic, social or psychological reasons
9. Patient under measure of legal protection
10. No social security \*For ethical reasons, the exclusion period within which the patient cannot be included in another trial will not be defined but discussed on a case to case basis.